T cells constitute about 60% of circulating blood leukocytes and play a central role in adaptive immunity. T cells recognise protein antigens complexed with MHC molecules through their T cell receptor-CD3 (“TCR/CD3”) complex. Naïve T cells need additional signals provided by professional antigen presenting cells (APCs), for example, CD28-CD80/86 interactions. It is well established that the triggering of the TCR is a central event in T cell activation and that ligation of additional co-stimulatory molecules is necessary for full stimulation of T cells.
Recently, TCR-independent methods of T cell activation have been disclosed. For example, the TCR-independent CD28 signal leads the selective transcription of survival (Bcl-xL) and inflammatory (IL-8 and B cell activation factor), but not proliferative (IL-2) genes, in a NFκB-dependent manner [1]. Further, ref. 2 teaches that, in the absence of TCR ligation, CD28 stimulation induced Th2 differentiation of memory, but not of naïve CD4(+) T cells.
It is an object of the invention to provide further and improved methods for TCR-independent T cell activation.